This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Xiang, H.
Right arrow Articles by Boxer, L. M.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Xiang, H.
Right arrow Articles by Boxer, L. M.

 Previous Article  |  Next Article 

Molecular and Cellular Biology, November 2006, p. 8599-8606, Vol. 26, No. 22
0270-7306/06/$08.00+0     doi:10.1128/MCB.01062-06
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

Role of the Cyclic AMP Response Element in the bcl-2 Promoter in the Regulation of Endogenous Bcl-2 Expression and Apoptosis in Murine B Cells{triangledown}

Hong Xiang, Jinghong Wang, and Linda M. Boxer*

Center for Molecular Biology in Medicine, Veterans Affairs Palo Alto Health Care System, and Department of Medicine, Stanford University School of Medicine, Stanford, California 94305

Received 13 June 2006/ Returned for modification 16 July 2006/ Accepted 5 September 2006

We have previously shown for B-cell lines that the cyclic AMP response element (CRE) is a major positive regulatory site in the bcl-2 promoter. However, the role of the CRE in the regulation of endogenous bcl-2 expression in vivo has not been characterized. We used gene targeting to generate knock-in mice in which a mutated CRE was introduced into the bcl-2 promoter region (mutCRE-bcl2 mice). Quantitative chromatin immunoprecipitation assays revealed that mutation of the CRE abolished the binding of CREB/ATF and CBP transcription factors to the bcl-2 promoter and greatly diminished the binding of NF-{kappa}B factors. The mutant CRE significantly reduced the expression of Bcl-2 in B cells and rendered them susceptible to surface immunoglobulin- and chemotherapeutic agent-induced apoptosis. The low levels of Bcl-2 were not changed with activation of the cells. The numbers of pre-B, immature B, and mature B cells in the bone marrow were decreased, as were the numbers of splenic B cells in mutCRE-bcl2 mice. Our findings indicate that the CRE in the bcl-2 promoter has an important functional role in the regulation of endogenous Bcl-2 expression and plays a critical role in the coordination of signals that regulate B-cell survival.

* Corresponding author. Mailing address: Hematology, CCSR 1155, Stanford University School of Medicine, 269 Campus Drive, Stanford, CA 94305-5156. Phone: (650) 849-0551. Fax: (650) 858-3982. E-mail: lboxer{at}stanford.edu.

{triangledown} Published ahead of print on 18 September 2006.

Molecular and Cellular Biology, November 2006, p. 8599-8606, Vol. 26, No. 22
0270-7306/06/$08.00+0     doi:10.1128/MCB.01062-06
Copyright © 2006, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Leich, E., Salaverria, I., Bea, S., Zettl, A., Wright, G., Moreno, V., Gascoyne, R. D., Chan, W.-C., Braziel, R. M., Rimsza, L. M., Weisenburger, D. D., Delabie, J., Jaffe, E. S., Lister, A., Fitzgibbon, J., Staudt, L. M., Hartmann, E. M., Mueller-Hermelink, H.-K., Campo, E., Ott, G., Rosenwald, A. (2009). Follicular lymphomas with and without translocation t(14;18) differ in gene expression profiles and genetic alterations. Blood 114: 826-834 [Abstract] [Full Text]  
  • Seo, H.-S., Liu, D. D., Bekele, B. N., Kim, M.-K., Pisters, K., Lippman, S. M., Wistuba, I. I., Koo, J. S. (2008). Cyclic AMP Response Element-Binding Protein Overexpression: A Feature Associated with Negative Prognosis in Never Smokers with Non-Small Cell Lung Cancer. Cancer Res. 68: 6065-6073 [Abstract] [Full Text]  
  • Kim, S.-J., Nian, C., Widenmaier, S., McIntosh, C. H. S. (2008). Glucose-Dependent Insulinotropic Polypeptide-Mediated Up-Regulation of {beta}-Cell Antiapoptotic Bcl-2 Gene Expression Is Coordinated by Cyclic AMP (cAMP) Response Element Binding Protein (CREB) and cAMP-Responsive CREB Coactivator 2. Mol. Cell. Biol. 28: 1644-1656 [Abstract] [Full Text]  
  • Aggarwal, S., Kim, S.-W., Ryu, S.-H., Chung, W.-C., Koo, J. S. (2008). Growth Suppression of Lung Cancer Cells by Targeting Cyclic AMP Response Element-Binding Protein. Cancer Res. 68: 981-988 [Abstract] [Full Text]  
  • Alejandro, E. U., Johnson, J. D. (2008). Inhibition of Raf-1 Alters Multiple Downstream Pathways to Induce Pancreatic -Cell Apoptosis. J. Biol. Chem. 283: 2407-2417 [Abstract] [Full Text]  
  • Paroni, G., Fontanini, A., Cernotta, N., Foti, C., Gupta, M. P., Yang, X.-J., Fasino, D., Brancolini, C. (2007). Dephosphorylation and Caspase Processing Generate Distinct Nuclear Pools of Histone Deacetylase 4. Mol. Cell. Biol. 27: 6718-6732 [Abstract] [Full Text]  


Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»